Universitaetsklinikum Heidelberg AöR
Verified
Heidelberg, Germany
Not recruiting
Effect of gut microbiome on tacrolimus pharmacokinetics with drug combination in healthy volunteers
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What is this trial about?
A plain-language summary of the goals, design and what participants do
The study examines how the gut microbiome, the community of bacteria living in the intestines, affects the way the drug tacrolimus is processed in the body. Tacrolimus is an immunosuppressant medication commonly used after organ transplants to keep the body from rejecting the new organ. A second medication, midazolam, is also given to compare how the body handles a different type of drug.
The purpose of the study is to compare the drug’s pharmacokinetics—how it is absorbed, distributed, metabolized, and eliminated—when volunteers have an unchanged microbiome versus after a short period of bowel cleansing that reduces the number of gut bacteria. Participants first receive tacrolimus in its regular immediate‑release form, and after a wash‑out period they receive a prolonged‑release tablet; blood samples are collected after each dose to measure drug levels.
During each phase, blood is drawn at several time points to calculate the total drug exposure, known as the AUC (area under the curve), and the highest concentration reached in the blood, called the Cmax. These measurements show how much of the drug is available to work in the body and how quickly it reaches its peak level. The study also records any side effects that occur while taking the medications.
The research process
The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.
Who can join the trial?
11 criteria
- Written informed consent that you sign and date before any study procedures begin.
- Willingness to follow any pandemic safety rules that may be in place during the study.
- Ability and willingness to understand and follow all study procedures and restrictions.
- Being between 18 and 59 years old at the time you sign the consent form.
- Having a body weight of at least 45 kilograms (about 99 pounds) when screened.
- If you could become pregnant, you must use a highly effective birth control method during the study and for 14 days after the last dose of the study drug, or you must be unable to become pregnant or be sexually abstinent.
- Agreeing to take part in a separate genetic test (study K093) to find out your CYP3A5 genotype, which is a gene that influences how the body processes certain medicines.
- Not having an ethnic background that commonly carries the CYP3A5*6 or CYP3A5*7 gene variations (these occur in more than 1 % of people in some groups).
- Having the specific genetic result called CYP3A5*3/*3 genotype, meaning you have two copies of the *3 version of this gene.
- Agreeing to follow the study’s specific dietary requirements, such as eating certain foods and avoiding others.
- Willingness to follow the rules needed for bowel cleansing, which includes special diet and fasting periods to clean out the intestines.
Who cannot join the trial?
25 criteria
- Significant medical problems found in your history, physical exam, or lab tests that need treatment or could stop you from finishing the study, or any condition that makes the study drug (called IMP) too risky.
- Use of any study drug (IMP) within 30 days before the first dose, or being enrolled in another drug or vaccine trial at the same time.
- Regular use of any medication (prescription, over‑the‑counter, or herbal) that cannot be stopped for the study, except hormonal birth control, iodine, and thyroid hormones; skin‑only (topical) medicines are okay if they don’t enter the bloodstream. Occasional use for headache or menstrual pain must be discussed with the investigator.
- Taking any substance that strongly increases drug‑metabolizing enzymes or transporters within 14 days before the first dose of tacrolimus or midazolam.
- Taking any substance that strongly blocks drug‑metabolizing enzymes or transporters within a period equal to five times the drug’s elimination half‑life before the first dose.
- Eating grapefruit within 7 days before the first dose or being unable to avoid grapefruit for the whole study; small amounts may be allowed if the investigator thinks they won’t affect the drug.
- Receiving a vaccination less than 2 weeks before the first dose (or less than 4 weeks for a live‑attenuated vaccine) or planning to get vaccinated during the study.
- Being unable or unwilling to avoid alcohol for 24 hours before the pharmacokinetic (PK) days, or having a problem with alcohol abuse.
- Being unable to avoid smoking during the study days.
- Testing positive for HIV (human immunodeficiency virus), hepatitis C, or hepatitis B surface antigen (HBsAg).
- Testing positive on the drug screening test at the screening visit.
- Having any acute or chronic illness that could change the gut microbiome (the community of bacteria in your intestines), such as an ongoing infection or significant gastrointestinal disorder.
- Being pregnant or breastfeeding.
- Being legally confined (for example, in a prison or psychiatric facility) or being legally unable to give consent.
- Taking antibiotics by mouth or IV within six weeks before the first dose.
- Having any acute or chronic illness or lab finding that could change how tacrolimus or midazolam is absorbed, distributed, metabolized, or removed from the body.
- Having a history of severe allergic ( anaphylactic ) reactions to drugs or vaccines, or other significant allergies.
- Being allergic to the study drugs, other macrolide antibiotics, or any ingredients in the study medication.
- Having any of the following lab results at screening:
- Low hemoglobin (<12 g/dL for men or <11 g/dL for women).
- Creatinine clearance less than 60 mL/min (a measure of kidney function).
- High total bilirubin (>1.2 × the normal upper limit; up to 3 × normal is allowed if Gilbert’s disease is suspected).
- High liver enzymes: ALT >1.1 × normal or AST >1.2 × normal.
- Abnormal thyroid‑stimulating hormone (TSH) unless explained by thyroid medication with normal free T4 (fT4) and free T3 (fT3) levels.
- Having glucose‑6‑phosphate dehydrogenase (G6PD) deficiency, either reported or detected in people from ethnic groups where it is common.
- Having a prolonged corrected QT interval (QTcF) greater than 440 ms for men or 460 ms for women (a heart rhythm measurement).
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Investigated drugs
Prograf
is a medication that contains tacrolimus, an immunosuppressant drug. In this study it is given as a concentrate that is mixed with fluid and given through an IV line. The purpose is to deliver tacrolimus directly into the bloodstream so the researchers can measure how the drug is absorbed and cleared when the gut microbiome is normal.
Prograf
(hard capsules) also contains tacrolusim, but it is taken by mouth as a capsule. This oral form lets the investigators see how tacrolimus is processed when it passes through the digestive system, both before and after the participants’ gut bacteria have been reduced.
Envarsus
is a prolonged‑release tablet that also contains tacrolimus. Because it releases the drug slowly over time, it helps the study team compare the long‑term absorption pattern of tacrolimus with the other forms, especially after the bowel‑cleansing preparation.
Dormicum
contains midazolam, a short‑acting sedative. It is used in the trial to keep participants comfortable during the IV infusion of tacrolimus, ensuring they remain relaxed and still while blood samples are taken.
MOVIPREP
is a bowel‑cleansing solution that contains a mixture of salts and a laxative called macrogol. Participants drink it to empty their intestines and dramatically lower the number of gut bacteria. This allows the researchers to compare tacrolimus levels before and after the gut microbiome has been reduced.
What is already known about the treatment
Prograf 5 mg/ml concentrate for infusion solution
This medication is given by intravenous infusion, where the concentrate is mixed with fluid and delivered into a vein. It is an approved drug that is widely used in medical practice and described in many studies. It is mainly used to prevent organ rejection after a transplant. It works by attaching to a protein inside immune cells, stopping an enzyme called calcineurin, which reduces the activity of the immune system; it belongs to the class of calcineurin inhibitors.
Prograf 5 mg hard capsules
This form is taken by mouth as a capsule. It is an approved and well‑known drug that appears in the medical literature for many years. It is used to prevent rejection of transplanted organs. The capsule releases tacrolimus, which binds to a protein in immune cells and blocks calcineurin, lowering the immune response; it is classified as a calcineurin inhibitor.
Dormicum® V 5 mg/5 ml injection solution
This product is administered by injection, usually into a vein or muscle. It is an approved medication that is commonly used and described in many clinical reports. It is used to produce sedation, relieve anxiety, and help with short procedures. The drug enhances the activity of the brain chemical GABA by binding to its receptors, leading to calmness; it belongs to the benzodiazepine class.
MOVIPREP Orange powder for oral solution
This preparation is mixed with water and drunk as a liquid. It is an approved laxative that is listed in drug references and used for bowel cleansing before procedures. It is used to clean the intestines before colon examinations or surgery. The powder contains substances that draw water into the bowel and a polymer that softens stool, creating an osmotic effect; it is classified as an osmotic laxative.
Envarsus 4 mg prolonged‑release tablets
This medication is swallowed as a tablet that releases the drug slowly over time. It is an approved product that is described in current medical literature for transplant patients. It is used to prevent organ rejection after transplantation. The tablet provides tacrolimus that binds to a cell protein and blocks calcineurin, reducing immune activity; it is a calcineurin inhibitor in a prolonged‑release form.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase ITrial ID2023-504405-37-00Protocol codeK806Estimated enrolment20 patientsSponsorUniversitaetsklinikum Heidelberg AöR
sourced from the EU Clinical Trials Register and site verification
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